In Situ Activation of Microencapsulated Drugs
- Created: Friday, 01 September 2000
Activation could be effected by thermal, electromagnetic, ultrasonic, and/or other forms of energy.
In a new method of delivering drugs to target sites in a human body, (1) the drugs would be stored in inactive forms in timed-release microcapsules that would be injected, then (2) the drugs would be activated by exposing the target sites to suitable forms of penetrating energy that could include electromagnetic radiation (radio waves, light, or x rays), ultrasound, or heat, then (3) the drugs would diffuse out of the microcapsules. The method would be well suited for drugs that have short shelf lives in their active forms and/or could be activated at target sites upon exposure to nonharmful activation energy.
The concept of microencapsulation of drugs was reported in "Microencapsulation of Multiple Drugs" (MSC-22489), NASA Tech Briefs, Vol. 20, No. 11 (November 1996), page 92. To recapitulate: microcapsules are formed as multilammelar, multiple-immiscible-phase structures that include alternating hydrophilic and hydrophobic liquid layers surrounded by flexible, semipermeable, polymeric outer membranes. The skins are designed to allow sustained diffusion of the bioactive drugs out of the microcapsules.
The disadvantage of conventional liposomes and of previously developed microcapsule drug-delivery systems is that they are impractical for delivery of drugs that are chemically labile or that have short shelf lives in their bioactive forms. Typically, a liposome or a previously developed microcapsule does not contain both a drug precursor and activator; consequently, the contents of the microcapsule cannot be converted to the active form of the drug immediately before or after administration to the patient. Also, conventional microcapsules cannot be lysed in situ to release bioactive drugs at target tissue sites without deposition of large amounts of energy that could adversely affect the tissues.
A microcapsule for use in the proposed method (see figure) would include a spherical drug-permeable outer membrane that would enclose immiscible fluid compartments containing the drug precursor in one phase and an activating agent in another phase. The activating agent would be a substance that could be activated by one of the forms of energy mentioned above and that would, in turn, react with the drug precursor to produce the active form of the drug. Such microcapsules would have to be protected from the activating form of energy during storage and until the time of administration to a patient.
Depending on the depth of the target site in the patient's body, the activating energy could be delivered from a transducer on the outside or, if necessary, from the inside by use of a catheter that contains a fiber-optic probe, ultrasonic or electromagnetic transducer, or other device. In a variation of the basic concept, the activating energy could also be utilized to stir the precursor and activator liquid phases together. In another variation, the activating agent could be contained within a thermosensitive membrane that could be ruptured to release the activating agent. Numerous other variations can readily be envisioned.
This work was done by Dennis R. Morrison of ohnson Space Center and Benjamin Mosier of Institute for Research, Inc. For further information, access the Technical Support Package (TSP) free on-line at www.nasatech.com/tsp under the Bio-Medical category.
This invention is owned by NASA, and a patent application has been filed. Inquiries concerning nonexclusive or exclusive license for its commercial development should be addressed to the Patent Counsel, Johnson Space Center, (281) 483-0837. Refer to MSC-22866.